Biomimetic Mineralization Research Articles

ZIF-8-decorated wood sponge derived from biomimetic mineralization of polydopamine

Zeolitic imidazolate framework-8 (ZIF-8) is extensively researched and used because of its exclusive structural and excellent physicochemical properties; however, significant challenges of alleviating the adverse effects of its particle form in many aspects are still faced by the scientific community. In this study, in situ growth of ZIF-8 within the pore channels and surfaces of green cellulose-based wood sponge was attempted through polydopamine-mediated incubation. The wood sponge was prepared by eliminating lignin and hemicellulose from natural balsa wood. Then, the sponge was impregnated with dopamine aqueous solution to yield polydopamine-covered wood sponge (PWS). ZIF-8 crystals were ultimately in situ grown in the substrate after sequential impregnation with zinc nitrate hexahydrate and 2-methylimidazole aqueous solutions at room temperature. Additionally, the effects of the deposition concentration of the dopamine aqueous solution and ZIF-8 incubation time were investigated. The obtained ZIF-8@PWS was characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, Brunauer–Emmett–Teller analysis and thermogravimetric analysis. Finally, the toluene adsorption performance of porous ZIF-8@PWS in aqueous solution was also briefly evaluated, and it was demonstrated that the maximum adsorption capacity was 106.4 mg/g and the removal rate was as high as 94.2%. This work validates the envisioned universal protocol of preparing ZIF-8-decorated porous substrates through the integrated mediating role of polydopamine.

Biomimetic mineralization engineered phycocyanin with improved stability and antioxidantive activity under environmental stress

Due to the brilliant blue color and antioxidative activity, phycocyanin (PC) has gained increased attentions in various fields. However, its high sensitivity towards environmental stress has greatly hindered the application of this elegant natural product. Incorporation of PC in a particulate form is an attractive strategy to maintain its functionalities. Herein, biomimetic mineralization was applied to fabricate PC@calcium phosphate (CaP) microparicles. The stability and antioxidative activity of PC@CaP was evaluated. It was disclosed that PC@CaP exhibited an enhancement in stability and antioxidative activity under environmental stress, signifying the role of the biomimetic mineralization in maintaining the stability and antioxidative activity of PC for its potential use in a variety of fields with high added-value.

Rapid Intrafibrillar Mineralization Strategy Enhances Adhesive–Dentin Interface

Biomimetic mineralization of dentin collagen appears to be a promising strategy to optimize dentin bonding durability. However, traditional postbonding mineralization strategies based on Ca/P ion release still have some drawbacks, such as being time-consuming, having a spatiotemporal mismatch, and having limited intrafibrillar minerals. To tackle these problems, a prebonding rapid intrafibrillar mineralization strategy was developed in the present study. Specifically, polyacrylic acid–stabilized amorphous calcium fluoride (PAA-ACF) was found to induce rapid intrafibrillar mineralization of the single-layer collagen model and dentin collagen at just 1 min and 10 min, as identified by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. This strategy has also been identified to strengthen the mechanical properties of demineralized dentin within a clinically acceptable timeframe. Significantly, the bonding strength of the PAA-ACF–treated groups outperformed the control group irrespective of aging modes. In addition, the endogenous matrix metalloproteinases as well as exogenous bacterial erosion were inhibited, thus reducing the degradation of dentin collagen. High-quality integration of the hybrid layer and the underlying dentin was also demonstrated. On the basis of the present results, the concept of “prebonding rapid intrafibrillar mineralization” was proposed. This user-friendly scheme introduced PAA-ACF–based intrafibrillar mineralization into dentin bonding for the first time. As multifunctional primers, PAA-ACF precursors have the potential to shed new light on prolonging the service life of adhesive restorations, with promising significance.

Enzymatic Nanomotors Surviving Harsh Conditions Enabled by Metal Organic Frameworks Encapsulation.

Enzyme-driven micro/nanomotors (MNMs) have demonstrated potentials in the biomedical field because of their excellent biocompatibility, versatility, and fuel bioavailability. However, the fragility of enzymes limits their practical application, because of their susceptibility to denaturation and degradation in realistic scenarios. Herein, a simple yet versatile and effective approach is reported to preserve the enzymatic activity and propulsion capability of enzymatic MNMs under various harsh conditions using metal organic frameworks (MOFs) as a protective shell. Urease can be encapsulated within the exoskeleton of zeolitic imidazolate framework-8 (ZIF-8) via biomimetic mineralization to form ZIF-8@urease (ZU-I) nanomotors that exhibit self-propulsion in the presence of urea. When exposed to harsh conditions, including high temperature, presence of proteases, and organic solvents, the ZU-I nanomotors still maintained their activity and mobility, whereas ZIF-8 with externally modified urease (ZU-O) nanomotors with externally modified urease as a control rapidly lost their motion capabilities owing to the inactivation of urease. Furthermore, ZU-I nanomotors exhibit effectively enhanced diffusion within the small intestine fluid, achieving a fourfold higher mucus penetration than the ZU-O nanomotors. The results highlight the effectiveness of using MOFs as protective shells for enzyme nano-engines, which can greatly advance the practical applications of enzymatic MNMs under realistic conditions, especially for biomedical purpose.

A convergent fabrication of graphene oxide/silk fibroin/hydroxyapatite nanocomposites delivery improved early osteoblast cell adhesion and bone regeneration

For controlled bone regeneration, two-dimensional materials are essential because they provide an isolated area for bone regeneration and protect the surrounding tissues. Excellent mechanical and hydrophilic qualities have made graphene oxide (GO) a common choice for bone regeneration. A biomimetic mineralization process combined with one-step vacuum filtering created mechanically strong and biocompatible two-dimensional (2D) membranes. Silk fibroin (SF) and hydroxyapatite (HA) increased the membranes' mechanical strength and hydrophilicity on the surface. Osteoblast adhesion, differentiation, and mineralization improved with little HA administered. A calvarial defect model was used to test the impact of the produced composite membranes on bone formation in vivo after they were implanted. Histological examination demonstrates that bone regeneration may be accelerated by GO/SF/HA composite membranes without needing endogenous cytokines. GO/SF/HA nanocomposite membranes with distinctive porous architectures, exceptional mechanical characteristics, and excellent bone regeneration capability are viable nanocomposites for bone regeneration.

Yolk-Shell Encapsulation of Cells by Biomimetic Mineralization and Visible Light-Induced Surface Graft Polymerization.

The pursuit of low-cytotoxicity modification strategies represents a prominent avenue in cell coating research, holding immense significance for the advancement of practical living cell-related technologies. Here, we presented a novel method to fabricate encapsulated yeast cells with a yolk-shell structure by biomimetic mineralization and visible-light-induced surface graft polymerization. In this approach, an amorphous calcium carbonate (ACC) shell was first deposited on the surface of a yeast cell (cell@ACC) modified with 4 layers of self-assembled poly(diallyl dimethylammonium chloride) (PDADMAC)/poly(acrylic acid) (PAA) film using a biomimetic mineralization technique. Subsequently, polyethylenimine (PEI) was absorbed on the surface of cell@ACC by electrostatic interaction. Then, a cross-linked shell was introduced by surface-initiated graft polymerization of poly(ethylene glycol) diacrylate (PEGDA) on cell@ACC under irradiation of visible light using thioxanthone catechol-O,O'-diacetic acid as the photosensitizer. After the removal of the inner ACC shell, the yolk-shell-structured yeast cells (cell@PHS) were obtained. Due to the mild conditions of the strategy, the cell@PHS could retain 98.81% of its original viability. The introduction of the shell layer significantly prolonged the lag phase of yeast cells, which could be tuned between 5 and 25 h by regulating the thickness of the shell. Moreover, the cell@PHS showed improved resistance against lyticase due to the presence of a protective shell. After 30 days of storage, the viability of cell@PHS was 81.09%, which is significantly higher than the 19.89% viability of native yeast cells.

Production of Functional Materials Derived from Regenerated Silk Fibroin by Utilizing 3D Printing and Biomimetic Enzyme-induced Mineralization

Production of Functional Materials Derived from Regenerated Silk Fibroin by Utilizing 3D Printing and Biomimetic Enzyme-induced Mineralization

Promoting effect of proanthocyanidin-amorphous calcium phosphate nanoparticles on biomimetic mineralization of demineralized dentin

Biomimetic mineralization is a new strategy for dentin repair emerging in the field of minimally invasive dentistry in recent years. However, the degradation of collagen fibrils and the lack of sustained supply of calcium and phosphorus ions are two main limitations during dentin biomimetic mineralization. Herein, by integrating the dual effects of collagen protection and mineralization induction, we proposed a novel nanoscale platform called proanthocyanidin-amorphous calcium phosphate nanoparticles (PA-ACP/NPs), which were solid nanospheres with uniform size and good biocompatibility, and could continuously release Ca and P ions in neutral or weak acidic microenvironment. PA-ACP/NPs effectively decreased the endogenous collagenase activity of demineralized dentin matrix and protected demineralized dentin collagen from degradation. Compared with the control ACP/NPs, PA-ACP/NPs induced nearly complete intrafibrillar mineralization of collagen fibrils and facilitated remineralization of demineralized dentin. As an additive of dental adhesives for the preliminary exploration of clinical application forms, the adhesive containing 20 wt% PA-ACP/NPs induced biomimetic intrafibrillar mineralization within the bonding interface after one and three months. PA-ACP/NPs nanoscale delivery exhibits excellent effects on stabilizing collagen fibrils and provides a long-term supply of mineral ions for dentin biomimetic mineralization, being a promising strategy for dentin biomimetic repair.

Progress in the Application of Biomimetic Mineralization for Tooth Repair

The tooth, including enamel and dentin, is a prominent biomineral that is produced by the biomineralization of living organisms. Although the mechanical performance of the tooth is outstanding, caries easily develop in a complex oral environment. The analysis of the chemical composition and the relationship between the mechanical properties and the structure is of great importance in solving caries. In this review, the multilevel structure and mechanical properties of enamel and dentin are briefly introduced, along with caries formation and the limitations of clinical dental restoration. Furthermore, the progress of the application of a wide range of biomimetic strategies for tooth remineralization is highlighted, including the use of calcium phosphate ionic clusters to construct the mineralization front, ensuring the oriented epitaxial growth of enamel crystals and replicating the complex structure of the enamel. Moreover, compared with the current clinical treatment, in which the resin composite and glass ionomer cement are the main repair materials and the high incidence of secondary caries leads to imperfect restorations, the remineralization tactics could achieve excellent repair effectiveness in reconstructing the complicated structure, restoring mechanical strength and gaining permanent repair. A basic understanding of enamel and dentin, their potential for restoration, and hopeful prospects for tooth repair that can be applied in the clinical setting, not just in the laboratory, is provided by this review.

Bacteria-templated ZIF-8 embedded in polyacrylonitrile nanofibers as a novel sorbent for thin film microextraction of benzoylurea insecticides

In the present work, the rod-like ZIF-8 (ZIF8@E coli) was prepared by fast, easy and environmentally friendly method of biomimetic mineralization with Escherichia coli bacteria as a bio-template and was exploited for the first time in the microextraction. In this regard, electrospun nanofiber mats of polyacrylonitrile (PAN) and ZIF8@E coli were prepared by electrospinning method and used as a new sorbent for thin film microextraction (TFME) of benzoylurea insecticides such as Hexaflumuron and Teflubenzuron as model analytes. The PAN/ZIF8@E coli nanocomposite was characterized using electron scanning microscopy and various spectroscopy techniques. Factors affecting the proposed extraction method were screened and optimized using the experiment design strategy. Then, the model analytes were measured by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detector after microextraction. Satisfactory figures of merit were obtained for suggested TFME-HPLC-UV under optimum conditions. The suitable linearity varied in the range of 0.5–200 μg L−1 with R2 greater than 0.9968. The limit of detections for Hexaflumuron and Teflubenzuron were 0.12 and 0.15 μg L−1, respectively. The application of the method in the real sample was investigated by analyzing the selected analytes in environmental water and food samples. The spiking recovery of the selected analytes varied in the range of 93.0–109.8 % (RSD≤7.68). The results confirm the efficient application of this new sorbent in TFME approach. Considering the high availability, ease of production, and environmental friendliness of bacteria along with the significant improvement of metal-organic framework (MOF) growth efficiency, biomimetic mineralization is expected to be efficient method for the synthesis of ordered MOFs for use in extraction fields.

Biomineralized ceria nanoparticles target the heart to improve diabetic cardiac remodeling by regulating mitochondrial oxidative stress and decreasing excessive mitophagy

Abstract Background An altered state of cardiomyocytes due to high glucose concentrations results in cell hypertrophy, leading to diabetic cardiomyopathy (DCM).The molecular regulatory process of mitochondrial dyshomeostasis and mitophagy, oxidative stress, and reactive oxygen species (ROS) production in diabetes is still not fully understood. Mitochondrial dyshomeostasis and mitophagy could be critical factors in the heart remodeling that occurs in diabetes. Purpose Our transcriptome sequencing of heart tissue revealed upregulation of the gene encoding the transferrin receptor (TfR) in the diabetic rat (Figure 1A). We then validated in vitro that high glucose increased TfR protein expression in the HL-1 cell line (Figure 1B). Herein, we developed a novel therapeutic ceria nanoparticle via biomineralization using transferrin (Tf) protein as a temple and assessed its targeted therapy for DM-induced cardiac remodeling via Tf-TfR mediated endocytosis. Method We synthesized Tf protein-based ceria NPs (CeO2@Tf) via biomineralization. Then the physicochemical and biological properties of NPs were characterized. Cellular uptake, cytotoxicity test, intracellularmitochondrial membrane potential (MMP), and ROS were verified with mouse cardiomyocytes HL-1 cells line. Afterward, the male C57BL/6N mice were randomly divided into control, DM, DM+Metformin (Met), and DM+NPs groups with eight weeks of treatment. Heart structure and function were measured by echocardiographic. The heart tissues were stained with hematoxylin, eosin (H&E), and Masson's trichrome stain to observe morphological changes and fibrosis. Western blot was used to determine mitochondrial homeostasis regulation-related proteins and mitophagy pathway. Results TEM and X-ray photoelectron spectroscopy characterized the properties successfully. MTT assay shows that HL-1 cell viabilities were not influenced by CeO2@Tf at 200 µM.High-glucose treatment led to increased ROS and decreased intracellular MMP in HL-1 cells. DM mice cardiac transcriptome sequencing results showed upregulation of transferrin receptor gene expression. Echocardiographic showed increased LAD and abnormal diastolic and systolic functions. All these abnormal changes were improved in the DM+ Met and DM+NPs groups. Our investigations revealed proteins linked to the PINK1-Parkin signaling pathway (Figure 2A-B) and found that the level of mitophagy in the diabetic group was overly high, which was improved after the application of CeO2@Tf. We observed the mitochondrial autophagosomes through transmission electron microscopy (Figure 2C). The autophagosomes in the diabetic group increased significantly and improved after treatment with CeO2@Tf. Conclusions These consistent biochemical and histopathological results suggest that the biomimetic mineralization of CeO2@Tf could inhibit oxidative stress and improve mitochondrial function in vitro induced by high-glucose and in vivo caused by DM, alleviating cardiac remodeling in DM mice.

Biomimetic nanozymes target the heart to suppress ferroptosis for ameliorating doxorubicin-induced cardiotoxicity via synergetic effect of antioxidant stress and Nrf2/Hmox1 inhibition

Abstract Background Doxorubicin (DOX) is the first-line standard treatment of numerous cancer. However, DOX may lead to irreversible degenerative cardiomyopathy, congestive heart failure, and various arrhythmias, known as doxorubicin-induced cardiotoxicity (DIC), which limits the clinical applications. Studies reported that ferroptosis plays an important role on the development of DIC. Targeted intervention of ferroptosis with the specific inhibitors, such as ferrostatin-1 (Fer-1), could effectively prevent DIC. In recent years, catalytic nanozymes, such as cerium oxide (CeO2), have received much attention due to their strong antioxidant properties. Purpose Our previous research found that the transferrin receptor (TfR) protein expression was significantly upregulated in DIC mice (Figure 1) . In this study, we synthesized a biomimetic CeO2-based nanozyme by biomineralization with transferrin (Tf) proteins as the template, and then we assessed its targeted therapy for DIC via Tf-TfR mediated endocytosis. Method Cellular uptake, cytotoxicity test, intracellularmitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial ferrous ions and lipid peroxidation toxicity were verified with rat cardiomyocytes line H9c2 cells. Afterward, the male C57BL/6N mice were randomly divided into control, DOX, DOX+Fer-1, and DM+NPs groups. Heart structure and function were measured by echocardiographic, electrocardiography and epicardial electrical labeling. Western blot determine mitochondrial homeostasis regulation-related proteins and Nrf2/Hmox1 signalling pathway. Finally, the biodistribution and biocompatibility of CeO2@Tf was assessed. Results Transmission electron microscopy images revealed the encapsulated CeO2@Tf was≈ 5 nm in diameter. The nanozyme significantly reversed cardiac structural and electrical remodeling and reduced myocardial necrosis. Meanwhile, RNA sequencing of ventricular tissue revealed increased cardiac Hmox1 mRNA levels in DIC mice (Figure 2). Further, it demonstrated that nanozyme intervention not only significantly suppressed the oxidative stress, mitochondrial lipid peroxidation and mitochondrial membrane potential damage, but also inhibited activation of Nrf2/Hmox1 signalling pathway to restore mitochondria-dependent ferroptosis. Furthermore, the nanozyme could be cleared by the hepatobiliary systems, and showed a good biocompatibility. Conclusions The current study showed that biomimetic mineralization of hybrid CeO2-based nanozyme against DIC were mediated by effect of antioxidant stress and the inhibition of Nrf2/Hmox1 signalling pathway, thereby maintaining mitochondrial homeostasis and function, and re-storing mitochondria-dependent ferroptosis. Furthermore, the nanozyme could be a promising prevention and treatment candidate for clinical translation as a novel cardiomyocyte ferroptosis protector to mitigate DIC and improve the prognosis and quality of life of cancer patients.

Graphene Oxide Functionalized Gelatin Methacryloyl Microgel for Enhanced Biomimetic Mineralization and in situ Bone Repair.

The formation of bone-like apatite (Ap) on natural polymers through biomimetic mineralization using simulated body fluid (SBF) can improve osteoconductivity and biocompatibility, while lowering immunological rejection. Nonetheless, the coating efficiency of the bone-like Ap layer on natural polymers requires improvement. Carbonyls (-COOH) and hydroxyls (-OH) are abundant in graphene oxide (GO), which may offer more active sites for biomimetic mineralization and promote the proliferation of rat bone marrow stromal cells (BMSCs). In this study, gelatin methacryloyl (GelMA) microgels were infused with GO (0, 0.5, 1, and 2 mg/mL) and embedded into microgels in SBF for 1, 7, and 14 days. Systematic in vitro and in vivo experiments were performed to evaluate the structure of the microgel and its effect on cell proliferation and ability to repair bone defects in rats. The resulting GO-GelMA-Ap microgels displayed a porous, interconnected structure with uniformly coated surfaces in bone-like Ap, and the Ca/P ratio of the 1 mg/mL GO-GelMA-Ap group was comparable to that of natural bone tissue. Moreover, the 1 mg/mL GO-GelMA-Ap group exhibited a greater Ap abundance, enhanced proliferation of BMSCs in vitro and increased bone formation in vivo compared to the GelMA-Ap group. Overall, this study offers a novel method for incorporating GO into microgels for bone tissue engineering to promote biomimetic mineralization.

Tunable Stress Relaxing Biomimetic Matrices: Hyaluronan/Hydroxyapatite Hybridization Mediates Assembly of Collagen Fibrils.

The alluring correlations of cellular behaviors with viscoelastic extracellular matrices have driven increasing endeavors directed toward the understanding of mechanical cues on cell growth and differentiation via preparing biomimetic scaffolds/gels with viscoelastic controllability. Indeed, systematic investigations, especially into calcium phosphate-containing biomimetics, are relatively rare. Here, oxidized hyaluronic acid/hydroxyapatite hybrids (OHAHs) were synthesized by hyaluronan-mediated biomimetic mineralization with confined ion diffusion and subsequent oxidization treatment. The collagen self-assembly was applied to fabricate tunable stress relaxing fibrillar matrices in the presence of OHAHs in which the incorporated hyaluronic acid with aldehyde groups acted to improve the component compatibility as well as to supplement the molecular interactions with the occurrence of a Schiff-base reaction. With the addition of varying OHAH contents, the self-assembly behavior of collagen was altered, and the obtained collagen-hybrid (CH) matrices presented a heterogeneous fibrillar structure interspersed with OHAHs, characterized by large fibrillar bundles coexisting with small fibrils. The OHAHs improved the hydrogel stability of pure collagen, and according to rheological and nanoindentation measurements, CH matrices also exhibited tunable stress relaxation rates, following an OHAH concentration-dependent fashion. The proliferation and spreading of MC3T3-E1 cells cultured onto such CH matrices were further found to increase with the stress relaxing rate of the matrices. The present study showed that the introduction of hydroxyapatite incorporated with active hyaluronic acid during collagen reconstitution was a simple and effective strategy to realize the preparation of tunable stress relaxing biomimetic matrices potentially used for further appraising the regulation of mechanical cues on cell behaviors.

Biomimetic Intrafibrillar Mineralization of Native Tendon for Soft-Hard Interface Integration by Infiltration of Amorphous Calcium Phosphate Precursors.

Soft and hard tissues possess distinct biological properties. Integrating the soft-hard interface is difficult due to the inherent non-osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c-axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.

Manganese Mineralization of Pathogenic Viruses as a Universal Vaccine Platform.

Biomimetic viral mineralization improves viral vaccine stability and immunogenicity using inorganic metals such as Ca, Al, or Fe. Mn is a metal found in high concentrations in mammalian tissues; however, under natural or laboratory conditions, Mn mineralization by medical viruses has yet to be established. Herein, a single IAV particle is successfully encapsulated with manganese phosphate (MnP) under specific conditions using the human influenza A virus (IAV). MnP-mineralized IAVs (IAV@Mn) exhibited physiochemical and in vitro properties similar to Ca-mineralized IAVs. In animal models, IAV@Mn shows limited replication in immune-competent cells and a significant attenuation compared to naïve cells. Moreover, a single-dose vaccination with IAV@Mn induced robust humoral and cellular immune responses and conferred significant protection against a wild-type IAV challenge in mice. Thus, Mn mineralization in pathogenic viruses provides a rapid and universal strategy for generating an emergency vaccine in response to emerging viruses.

Biomimetic synthesis of polydopamine-graphene oxide/hydroxyapatite for efficient and fast uranium(VI) capture from aqueous solution.

A novel and efficient mesoporous nano-absorbent for U(VI) removal was developed through an environment-friendly route by inducing the biomimetic mineralization of hydroxyapatite (HAP) on the bioinspired surface of polydopamine-graphene oxide (PDA-GO). PDA-GO/HAP exhibited the greatly rapid and efficient U(VI) removal within 2 min, and much higher U(VI) adsorption capacity of 433.07 mg·g-1 than that of GO and PDA-GO. The enhanced adsorption capacity was mainly attributed to the synergistic effect of O-H, -C=N-, and PO43- functional groups and the incorporation of uranyl ions by the formation of a new phase (chernikovite, H2(UO2)2(PO4)2·8H2O). The adsorption process of U(VI) fitted well with pseudo-second-order kinetic and Langmuir isotherm model. Moreover, PDA-GO/HAP showed a high U(VI) adsorption capacity in a broad range of pH values and owned good thermal stability. PDA-GO/HAP with various excellent properties made it a greatly promising adsorbent for extracting uranium. Our work developed a good strategy for constructing fast and efficient uranium-adsorptive biomimetic materials.

A Biomimetic Se-nHA/PC Composite Microsphere with Synergistic Immunomodulatory and Osteogenic Ability to Activate Bone Regeneration in Periodontitis.

Accumulation of reactive oxygen species (ROS) in periodontitis exacerbates the destruction of alveolar bone. Therefore, scavenging ROS to reshape the periodontal microenvironment, alleviate the inflammatory response and promote endogenous stem cell osteogenic differentiation may be an effective strategy for treating bone resorption in periodontitis. In this study, sericin-hydroxyapatite nanoparticles (Se-nHA NPs) are synthesized using a biomimetic mineralization method. Se-nHA NPs and proanthocyanidins (PC) are then encapsulated in sericin/sodium alginate (Se/SA) using an electrostatic injection technique to prepare Se-nHA/PC microspheres. Microspheres are effective in scavenging ROS, inhibiting the polarization of macrophages toward the M1 type, and inducing the polarization of macrophages toward the M2 type. In normal or macrophage-conditioned media, the Se-nHA/PC microspheres effectively promoted the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Furthermore, the Se-nHA/PC microspheres demonstrated anti-inflammatory effects in a periodontitis rat model by scavenging ROS and suppressing pro-inflammatory cytokines. The Se-nHA/PC microspheres are also distinguished by their capacity to decrease alveolar bone loss, reduce osteoclast activity, and boost osteogenic factor expression. Therefore, the biomimetic Se-nHA/PC composite microspheres have efficient ROS-scavenging, anti-inflammatory, and osteogenic abilities and can be used as a multifunctional filling material for inflammatory periodontal tissue regeneration.

Glucose-responsive enzymatic biomimetic nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic anticancer therapy

Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H2O2 at the tumor site. More importantly, the self-supplied peroxide hydrogen (H2O2) can convert ABTS (2,2′-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe2+ arising from the reduction of Fe3+ by overexpressed GSH reacts with H2O2 to generate intensely reactive •OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies. Statement of significanceCombinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H2O2. The self-supplied H2O2 initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous •OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy.

Unveiling the composition of hydroxyapatite minerals and their (bio)-organic adlayer using X-ray photoelectron spectroscopy

Although X-ray photoelectron spectroscopy (XPS) is a surface science technique, it is widely used for chemical analysis of hydroxyapatite (HAP) minerals. The use of biomimetic mineralization strategies further complicates the chemical context with possible adsorption of biomolecules. This work addresses methodological developments dealing with the reliability of XPS data and their interpretation on series of HAPs yielding variable amounts of carbonate and fluoride and different (bio)-organic adlayers. A specific focus is given here to: selectivity (adsorbed bio-organic compounds and inorganic constituents), precision (generation of statistically meaningful data) and accuracy (differential screening effects and factors influencing the quantification) of XPS data. Results show that exploring the information acquired for the (bio)-organic adlayer allows (i) to make a distinction between oxygen of organic and inorganic nature and (ii) to consider a differential screening effect. When exploring correlations between spectra guided by stoichiometry and charge balance, significant discrepancies are observed when quantifying phosphorus through the P 2p or the P 2s peak. The O/P ratio is shown to usefully evaluate the consistency of XPS data, while the interpretation of the Ca/P ratio with respect to surface chemistry should be approached cautiously, as quantification may require corrections that are rarely considered.